Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p<0.01), while it reduced 300μM acetylcholine (ACh) (p<0.01), 100μM veratridine (Ver) (p<0.01) and 56mM K(+) (p<0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p<0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56mM K(+) induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p<0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p<0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects.
BackgroundMenopause is characterized by a decrease in life quality due to the appearance of uncomfortable symptoms. Nowadays, Understanding menopause-associated pathophysiology and developing new strategies to improve the treatment of menopausal-associated symptoms is an important issue. Our study was to evaluate the synergistic effects of Danshen (salvia miltiorrhiza bunge) and the phytoestrogenic effects of 3 modified Qing E formulas, to explore a better formula for menopausal disorders.Methods100 rats were randomized into 5 groups: Sham (Sham operation group), OVX (model group of ovariectomized rat), BDL (group with low concentration of Qing E Formula), BDH (group with high concentration of Qing E Formula) and BDD (group with high concentration of Qing E Formula Plus Danshen), receiving vehicle and extract of different modified Qing E formula respectively. The food intake, body weight, uterus weight, blood levels of triglycerides (TG), total cholesterol (TC) and cholesterol fractions were assessed. The mammary glands and uterus were morphologically analyzed. The bone density of tibias were measured by peripheral quantitative computed tomography (pQCT). Additionally, luciferase induction assays were performed in Hela cells with the mixtures derived from Qing E formula plus Danshen (BDD).ResultsQing E formula plus Danshen significantly increased the uterus wet weight, enhanced the thickness of uterine wall, endometrial epithelium and glandular epithelium, improved trabecular bone and total density evidently, reduced the levels of low density lipoprotein cholesterol (LDL-C) and TG, possessed notable estrogen receptor beta (ERβ) and estrogen receptor alpha (ERα) agonist activity.ConclusionQing E formula plus Danshen exerted more evident estrogen-like effects, thus it has a potential therapeutic use to treat menopausal disorders.
Summary Background Topical retinoids are effective in retarding skin ageing and restoring homeostasis in skin conditions such as psoriasis. However their adverse effects (AEs), which include irritation (retinoid dermatitis), photosensitivity and teratogenicity, limit their use and patient compliance. Development of retinoid analogues with minimal AEs would allow a broader and more compliant use. Aim To synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a modulatory gene expression profile similar to retinoids, using as reference three prescription retinoids: tretinoin, tazarotene and adapalene. Methods We hypothesized that because bakuchiol salicylate has a structure entirely different from existing retinoids, there would be at least a partial uncoupling of AEs from the skin normalizing activity of this retinoid. This hypothesis was tested at the transcriptional level in psoriatic cytokine-treated cultures of keratinocytes and organotypic skin substitutes, using DNA microarrays and custom PCR arrays. Results Evaluation of the gene expression profile of bakuchiol salicylate revealed elimination of several components of the retinoid-like proinflammatory response and teratogenic signature, without a substantial loss of normalizing potential. A possible mechanism of action, consisting of keratinocyte desensitization to psoriatic cytokine signalling through the inhibition of the signal transducer and regulator of transcription (STAT)1/3/interferon inflammatory signal transduction axis was also identified. Conclusion Bipartite materials obtained by merging two skin-active entities with specific, complementary bioactivities, such as bakuchiol and salicylic acid, may yield a new class of functional retinoids.
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